Top Level Name

  ⌊ Superfamily (core) Radical SAM

Family known
Total 100% <100% Family unknown
Functional domains 113776 55708 581 57487
UniProtKB 315576 177211 923 137442
GI 590483 331820 2053 256610
Structures 72
Reactions 85
Functional domains of this superfamily were last updated on Nov. 22, 2017
New functional domains were last added to this superfamily on Sept. 14, 2016

The Radical SAM enzymes all utilise S-adenosylmethionine as a source of an organic 5'-deoxyadenosyl radical. This radical species is the same as that found in the cobalamin-dependent enzymes and are found across all Kingdoms of life.

The Radical SAMs all have a conserved three cysteine motif (commonly CxxxCxxC) that binds a [4Fe-4S]+ cluster, responsible for the activation of the SAM. This iron-sulfur cluster is unique in that one of the irons are unsatisfied by protein ligands, and instead ligates the SAM in a bidentate manner. They all activate SAM in an identical manner. However, that is where the similarity ends, and they catalyse a wide variety of different overall chemistries.

(Radical SAM Workshop Materials)

Vey JL, Drennan CL.

Structural insights into radical generation by the radical SAM superfamily

▸ Abstract

Chem Rev. 2011;111(4):2487-2506 | PubMed ID: 21370834

Frey PA, Hegeman AD, Ruzicka FJ.

The Radical SAM Superfamily

▸ Abstract

Crit Rev Biochem Mol Biol. 2008;43(1):63-88 | PubMed ID: 18307109

Sofia HJ, Chen G, Hetzler BG, Reyes-Spindola JF, Miller NE

Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods

▸ Abstract

Nucleic Acids Res 2001;29(5):1097-1106 | PubMed ID: 11222759

Dowling DP, Vey JL, Croft AK, Drennan CL

Structural diversity in the AdoMet radical enzyme superfamily

▸ Abstract

Biochim Biophys Acta 2012;1824(11):1178-1195 | PubMed ID: 22579873

Banerjee R

Introduction to the Thematic Minireview Series: Radical SAM Enzymes

▸ Abstract

J Biol Chem 2014;None(None):None-None | PubMed ID: 25477525

Stich TA, Myers WK, Britt RD

Paramagnetic intermediates generated by radical S-adenosylmethionine (SAM) enzymes

▸ Abstract

Acc Chem Res 2014;47(8):2235-2243 | PubMed ID: 24991701

Shibata N, Toraya T

Molecular Architectures and Functions of Radical Enzymes and Their (Re)activating Proteins

▸ Abstract

J Biochem 2015;None(None):None-None | PubMed ID: 26261050

Horitani M, Byer AS, Shisler KA, Chandra T, Broderick JB, Hoffman BM

Why Nature Uses Radical SAM Enzymes so Widely: Electron Nuclear Double Resonance Studies of Lysine 2,3-Aminomutase Show the 5'-dAdo• &quot;Free Radical&quot; Is Never Free

▸ Abstract

J Am Chem Soc 2015;137(22):7111-7121 | PubMed ID: 25923449

Ji X, Li Y, Xie L, Lu H, Ding W, Zhang Q

Expanding Radical SAM Chemistry by Using Radical Addition Reactions and SAM Analogues

▸ Abstract

Angew Chem Int Ed Engl 2016;55(39):11845-11848 | PubMed ID: 27573794

Broderick JB, Duffus BR, Duschene KS, Shepard EM

Radical S-adenosylmethionine enzymes

▸ Abstract

Chem Rev 2014;114(8):4229-4317 | PubMed ID: 24476342

Alignment taken from PFam seed alignment (PF04055) on the 2nd June 2014. Corresponding InterPro identifier is IPR007197.

1: Radical SAM Activation Step

Cofactor(s)

[4Fe-4S]+ Cluster (complex)

S-Adenosylmethionine (coenzyme)

Sequence Similarity Networks

Download a Sequence Similarity Network of this superfamily (XGMML format ).

Network downloads are XGMML files that are readable by program such as Cytoscape. In these networks, nodes represent proteins and edges represent pairwise similarities better than a given edge-score cutoff. The edge score is either a bit score for full networks or mean E values for a Repnet. Additionally, these networks contain several attributes with data from the SFLD.

Select any restriction to apply to your network.
Maximum number of edges:
250K 500K 750K ALL
edge-score cutoff

Full sequence similarity network is not available for this superfamily due to its size.
Repnet: 50% ID (11-May-2017)

List of files included in the download. A detailed list of included node attributes, their definitions, and their uses [revised: 1/24/2014].

Reaction Network

Download Reaction Network of this superfamily (XGMML format ).

Reaction Network downloads are XGMML files that are readable by program such as Cytoscape. In these networks, nodes represent proteins and edges represent pairwise similarities better than a given bitscore-cutoff. Additionally, these networks contain several attributes with data from the SFLD.

Only 40 of 85 Reactions for the Superfamily could be computed.

Reaction Network: 21-Dec-2016

Molecular Networks

Download Molecular Networks of this superfamily (XGMML format ).

Molecular Network downloads are XGMML files that are readable by program such as Cytoscape. In these networks, nodes represent molecules in a reaction and edges represent pairwise similarities better than a given bitscore-cutoff. Additionally, these networks contain several attributes with data from the SFLD.

Molecular Network: Superfamily (23-Jan-2017) Molecular Network: Superfamily substrate (23-Jan-2017) Molecular Network: Superfamily product (23-Jan-2017)

Disclaimer
Although the download speed has improved please keep in mind that network files can be quite large. We are currently working on improving the network download and finding ways to make large networks manageable. Please see How to increase memory for Cytoscape.

Multiple Sequence Alignment

View the alignment of a representative set of sequences of this superfamily using

Multiple Sequence Alignment

Align one or multiple sequences to the alignment of a representative set of sequences of this superfamily.
Enter FASTA formatted sequence(s) : and view results using

Downloads

Data Type All (#) Known (#) Unknown (#)
Full length FASTA (113776) (56289) (57487)
Complete annotation (.tsv) (113776) (56289) (57487)
Annotation suitable for Excel ® (.tsv) (113776) (56289) (57487)
Clear form

Some of these files can be quite large, please be patient during the download.

To identify your sequence later, please make sure to provide a header line starting with '>' for each sequence. Empty headers are allowed, but a header line is always required.
Cutoff Value
The least significant edge-score at which pairwise similarities are included in the network. A bit score for the full network, or a mean E value for the Repnet.
XGMML format
Open in Cytoscape via:
 Menu
 →Import
 →Network (multiple file types)
Download the annotation of all sequences as shown in the table below as a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application.
Full length FASTA
Full length sequences in FASTA format.
Functional Domain FASTA
Sequences of the Functional Domain in FASTA format.
Complete annotation
Download complete annotation of sequences sets of this superfamily as a ͟Tab ͟Separated ͟Value (TSV) file. This file has all data but cell size can exceed the maximum supported by spreadsheet programs (such as Microsoft Excel ®).
Spreadsheet ready annotation
Annotation of sequences sets of this superfamily in a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application. Cells which exceed the allowed spreadsheet maximum (32.5K) are preceded by the word "Truncated" and clipped short.
Total number of functional domains in this group.
Number of Functional Domains that have been manually or automatically been assigned to a family.
Number of Functional Domains that have not been assigned to a family.
Number of structures available from the PDB for members of this group.
Number of Functional Domains with 100% of Conserved Residues
Number of Functional Domains with less than 100% Conserved Residues
Subgroup ▸ Legend T K C U S
7-carboxy-7-deazaguanine synthase like 4126 1101 1099 3025 7
┗ 7-carboxy-7-deazaguanine synthase, Cx14CxxC type 509 509 509 5
┗ 7-carboxy-7-deazaguanine synthase, Cx3CxxC type 403 403 402 0
┗ ExsD-like 189 189 188 0
anaerobic coproporphyrinogen-III oxidase like 12939 2864 2857 10075 1
┗ cyclopropanase 18 18 18 0
┗ heme degradation proteins (HutW/ChuW-like) 36 36 36 0
┗ HemN-like, clustered with heat shock genes 285 285 283 0
┗ HemN-like, clustered with nucleoside-triphosphate RdgB 265 265 262 0
┗ oxygen-independent coproporphyrinogen-III oxidase 1 (HemN-like) 1423 1423 1421 1
┗ oxygen-independent coproporphyrinogen-III oxidase 2 (HemZ-like) 829 829 829 0
┗ 1: methyltransferase (class C) 18 8 8 10 0
┗ 3-methyl-2-indolic acid methyltransferase (NocN/NosN like) 3 3 3 0
┗ methylation of yatakemycin (YTK) 1 1 1 0
┗ pyrimidine ring methyltransferase (bleomycin-like antibiotic biosynthesis) 4 4 4 0
antiviral proteins 312 198 196 114 0
┗ Viperin 198 198 196 0
AviX12-like 7 3 3 4 0
┗ avilamycin epimerase 3 3 3 0
B12-binding domain containing 6858 1307 1304 5551 0
┗ anaerobic magnesium-protoporphyrin-IX monomethyl ester cyclase 91 91 90 0
┗ bacteriocin maturation 135 135 135 0
┗ hopanetetrol cyclitol ether synthase 212 212 212 0
┗ ladderane biosynthesis 4 4 4 0
┗ OxsB-like 1 1 1 0
┗ paromamine deoxygenase 3 3 3 0
┗ valine cyclopropanase 5 5 5 0
┗ 1: methyltransferase (Class B) 2002 858 856 1144 0
┗ 5''-pyrrole methytransferase 46 46 46 0
┗ bacteriochlorophyll C12 methyltransferase 17 17 17 0
┗ bacteriochlorophyll C8 methyltransferase 14 14 14 0
┗ carbapenem intermediate methyltransferase (ThnK-like) 3 3 3 0
┗ carbapenem intermediate methyltransferase (ThnL-like) 3 3 3 0
┗ carbapenem intermediate methyltransferase (ThnP-like) 2 2 2 0
┗ chondrochloren A methyltransferase (CndI-like) 2 2 2 0
┗ fortimicin-like methyltransferase 3 3 3 0
┗ gentamicin C-6' methyltransferase (GenK-like) 1 1 1 0
┗ gentamicin-like N-methyltransferase (GntE-like) 5 5 5 0
┗ hopanoid C2-methyltransferase (HpnP-like) 660 660 659 0
┗ hopanoid C3-methyltransferase (HpnR-like) 69 69 69 0
┗ P-methyltransferase (PhpK-like) 12 12 11 0
┗ pactamycin C-methyltransferase (PctJ-like) 2 2 2 0
┗ pactamycin C-methyltransferase (PctN-like) 2 2 2 0
┗ pactamycin methyltransferase (PctO-like) 2 2 2 0
┗ phosphonoacetaldehyde methylase (fom3-like) 4 4 4 0
┗ thioacetal methlytransferase (Swb9-like) 1 1 1 0
┗ tryptophan 2-C-methyltransferase 8 8 8 0
┗ 1: B12-binding methylthiotransferase like 33 0 0 33 0
BATS domain containing 8239 5779 5779 2460 25
┗ 1: cleavage of the Ca-Cb bond in aromatic amino acids 2304 2231 2231 73 4
┗ 2-iminoacetate synthase (ThiH) 1523 1523 1523 0
┗ 3-methyl-2-indolic acid synthase (NosL) 5 5 5 0
┗ [Fe] hydrogenase maturase (HydG-like) 703 703 703 0
┗ 1: biotin synthase like 5006 3245 3245 1761 1
┗ biotin synthase 3245 3245 3245 1
┗ 1: HMD cofactor maturase (HmdB-like) 39 39 39 0 0
┗ HMD cofactor maturase (HmdB-like) 39 39 39 0
┗ 1: HydE/PylB-like 886 264 264 622 20
┗ 3-methylornithine synthase (PylB-like) 42 42 42 1
┗ [FeFe] hydrogenase maturase (HydE-like) 222 222 222 10
DesII-like 12 12 12 0 0
┗ dTDP-4-amino-4,6-dideoxy-D-glucose ammonia-lyase (DesII-like) 12 12 12 0
elongater protein-like 2626 1038 1020 1588 2
┗ ELP3-like 1038 1038 1020 0
F420, menaquinone cofactor biosynthesis 3271 2540 2537 731 0
┗ 1: 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase 1109 1109 1107 0 0
┗ ((2,3,4,5-tetrahydroxypentyl)amino)dihydropyrimidine-2,4-dione synthase (CofH-like) 925 925 924 0
┗ 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase (CofG-like) 184 184 183 0
┗ 1: menaquinone synthsis involved 1794 1403 1402 391 0
┗ aminofutalosine synthase (mqnE-like) 534 534 534 0
┗ cyclic dehypoxanthine futalosine synthase (mqnC-like) 897 897 896 0
FeMo cofactor biosynthesis protein 813 796 784 17 0
┗ FeMo cofactor biosynthesis protein (nifB-like) 796 796 784 0
lipoyl synthase like 5416 5368 5331 48 5
┗ lipoyl synthase 5368 5368 5331 2
methylthiotransferase 14884 13235 13188 1649 2
┗ (dimethylallyl)adenosine tRNA methylthiotransferase (MiaB-like) 5191 5191 5179 0
┗ CDK5RAP1 903 903 903 0
┗ ribosomal protein S12 methylthiotransferase (RimO-like) 4166 4166 4143 2
┗ threonylcarbamoyladenosine tRNA methylthiotransferase 2975 2975 2963 0
methyltransferase (Class A) 6632 5918 5918 714 6
┗ adenosine C2 methyltransferase (RlmN-like) 5880 5880 5880 4
┗ adenosine C8 methyltransferase (Cfr-like) 38 38 38 0
methyltransferase (Class D) 572 171 158 401 0
┗ 7,8-dihydro-6-hydroxymethylpterin dimethylase 171 171 158 0
organic radical-activating enzymes 7847 7036 6966 811 3
┗ 4-hydroxyphenylacetate decarboxylase activase 7 7 7 0
┗ 1: activating enzymes, group 1 2732 2721 2721 11 0
┗ anaerobic ribonucleoside-triphosphate reductase activase 2721 2721 2721 0
┗ 1: activating enzymes, group 2 4657 4308 4238 349 3
┗ benzylsuccinate synthase activase 69 69 69 0
┗ glycerol dehydratase activase 5 5 5 0
┗ pyruvate formate-lyase activase 3653 3653 3612 3
┗ YjjI activase 581 581 552 0
PLP-dependent 2679 1836 1829 843 1
┗ arginine 2,3-aminomutase 26 26 26 0
┗ glutamate 2,3-aminomutase 72 72 71 0
┗ L-lysine 2,3-aminomutase (LAM-like) 402 402 401 1
┗ L-lysine 2,3-aminomutase (yjeK like) 1336 1336 1331 0
SPASM/twitch domain containing 18807 6060 5721 12747 10
┗ adenosyl-hopene transferase 539 539 533 0
┗ cytosylglucuronate decarboxylase 5 5 5 0
┗ KxxxW cyclic peptide maturase (StrB-like) 18 18 18 0
┗ neomycin C-like epimerase 4 4 4 0
┗ pcfB-like 1 1 0 0
┗ UDP-N-acetyl-tunicamine-uracil synthase (TunB-like) 4 4 4 0
┗ 1: main SPASM domain-containing 16026 5439 5109 10587 8
┗ coenzyme PQQ synthesis protein E (PqqE-like) 1061 1061 1034 0
┗ 2: dehydrogenase like 2360 1813 1693 547 4
┗ anaerobic Cys-type sulfatase-maturating enzyme 163 163 159 4
┗ anaerobic Ser-type sulfatase-maturating enzyme 1650 1650 1534 0
┗ 2: thioether bond formation requiring one auxiliary iron-sulfur cluster 126 107 107 19 0
┗ antilisterial bacteriocin subtilosin biosynthesis protein (AlbA-like) 49 49 49 0
┗ sporulation killing factor protein (SkfB-like) 6 6 6 0
┗ thuricin CD (TrnCD-like) 46 46 46 0
┗ thurincin H (ThnB-like) 6 6 6 0
┗ 2: cyclic pyranopterin phosphate synthase (MoaA-like) 6347 1760 1579 4587 4
┗ cyclic pyranopterin phosphate synthase (MoaA-like) 1760 1760 1579 4
┗ 2: thioether bond formation requiring two auxiliary iron-sulfur clusters 1448 113 112 1335 0
┗ quinohemoprotein amine dehydrogenase maturation protein (QhpD-like) 112 112 111 0
┗ Tte1186a maturase 1 1 1 0
┗ 2: heme carboxy lyase like 1827 586 585 1241 0
┗ alternative heme biosynthesis C (AhbC-like) 146 146 145 0
┗ alternative heme biosynthesis D (AhbD-like) 71 71 71 0
┗ C-terminal tyrosine decarboxylase (MftC-like) 181 181 181 0
┗ heme D1 biosynthesis (NirJ-like) 188 188 188 0
┗ 1: BtrN-like SPASM domain containing 756 49 47 707 2
┗ 2-deoxy-scyllo-inosamine dehydrogenase (BtrN-like) 10 10 9 2
┗ tungsten cofactor oxidoreducase radical SAM maturase 39 39 38 0
spectinomycin biosynthesis (SpcY-like) 6 2 2 4 0
┗ spectinomycin biosynthesis (SpcY-like) 2 2 2 0
spore photoproduct lyase like 437 290 290 147 8
┗ spore photoproduct lyase 1 188 188 188 6
┗ spore photoproduct lyase 2 102 102 102 0
tRNA wybutosine-synthesizing 793 735 714 58 2
┗ tRNA wybutosine-synthesizing 735 735 714 2
Uncharacterised Radical SAM Subgroup 1 860 0 0 860 0
Uncharacterised Radical SAM Subgroup 10 419 0 0 419 0
Uncharacterised Radical SAM Subgroup 11 180 0 0 180 0
Uncharacterised Radical SAM Subgroup 12 870 0 0 870 0
Uncharacterised Radical SAM Subgroup 14 1056 0 0 1056 0
Uncharacterised Radical SAM Subgroup 15 661 0 0 661 0
Uncharacterised Radical SAM Subgroup 16 212 0 0 212 0
Uncharacterised Radical SAM Subgroup 17 44 0 0 44 0
Uncharacterised Radical SAM Subgroup 19 114 0 0 114 0
Uncharacterised Radical SAM Subgroup 2 2635 0 0 2635 0
Uncharacterised Radical SAM Subgroup 20 81 0 0 81 0
Uncharacterised Radical SAM Subgroup 21 172 0 0 172 0
Uncharacterised Radical SAM Subgroup 22 167 0 0 167 0
Uncharacterised Radical SAM Subgroup 4 119 0 0 119 0
Uncharacterised Radical SAM Subgroup 5 314 0 0 314 0
Uncharacterised Radical SAM Subgroup 6 949 0 0 949 0
Uncharacterised Radical SAM Subgroup 7 815 0 0 815 0
Uncharacterised Radical SAM Subgroup 8 84 0 0 84 0
uncharacterized CHP01210-like 114 0 0 114 0
UPF0313 2611 0 0 2611 0
Depth of the multi-level Subgroup hierarchy.